Is ALK p.Arg1464fs (c.4390_4391insCA) pathogenic?

ALK p.Arg1464fs (c.43904391insCA) is classified Uncertain significance in ALK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). Associated with neuroblastoma, susceptibility to, 3.

What condition is associated with ALK p.Arg1464fs (c.4390_4391insCA)?

ALK p.Arg1464fs (c.4390_4391insCA) is associated with neuroblastoma, susceptibility to, 3 (ClinVar).

ALK p.Arg1464fs

c.4390_4391insCA · VCV3664923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neuroblastoma, susceptibility to, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (29 of 29) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.41	GERP -4.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ALK
Protein: p.Arg1464fs
Coding: c.4390_4391insCA
MANE Select: NM_004304
Type: Insertion
Location: chr2:29193696 (GRCh38)
Gene constraint: LOEUF 0.562 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.26 · 79 PDB

Full ALK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuroblastoma, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALK p.Arg1464Gln Uncertain significance ★★ ⚠ same residue
ALK p.Arg1464Gly Uncertain significance ★★ ⚠ same residue
ALK p.Arg1464Ter Uncertain significance ★★ same residue
ALK c.2487+4_2487+5insA Uncertain significance ★★ same condition
ALK p.Gly1201fs Uncertain significance ★★ same condition
ALK p.Val728_Pro729insTrpTrp Uncertain significance ★★ same condition
ALK p.235SP[3] Uncertain significance ★ same condition
ALK p.Arg1464Leu Uncertain significance ★ ⚠ same residue

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/alk-p-arg1464fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown